The effect of curcumin supplementation on endothelial function and blood pressure in patients with metabolic disorders: A meta-analysis of meta-analyses.

Several interventional studies have revealed the beneficial impact of curcumin supplementation on blood pressure and endothelial function, but the findings are conflicting. Therefore, this study was conducted to investigate the effects of curcumin supplementation on blood pressure and endothelial function. A meta-analyses of randomized clinical trials were performed by searching PubMed, Embase, Scopus, and Web of Science were searched up to March 31, 2024. Random effects models were used to calculate weighted mean differences (WMD). Pooled estimates of 10 studies revealed that curcumin decreased diastolic blood pressure (DBP) [WMD = -0.94, 95 % CI: -1.59, -0.30; p = 0.004], pulse wave velocity (PWV) [WMD = -45.60, 95 % CI: -88.16, -3.04; p = 0.03, I2 = 0.0 %, p = 0.59], and vascular cell adhesion molecule-1 (VCAM-1) [WMD = -39.19; 95 % CI: -66.15, -12.23, p =0.004; I2=73.0 %, p = 0.005] significantly, and increased flow-mediated dilation (FMD) [WMD = 1.64, 95 % CI: 1.06, 2.22; p < 0.001, I2 = 0.0 %, p = 0.61. However, curcumin did not significantly change systolic blood pressure (SBP) [WMD = -0.64, 95 % CI: -1.96, 0.67; p =0.34, I2 = 83.5 %, p <0.001], and Intercellular Adhesion Molecule 1 (ICAM1) [WMD = -17.05; 95 % CI: -80.79, 46.70, p =0.601; I2=94.1 %, p < 0.001]. These results suggest that curcumin has a beneficial effect on DBP, PWV, VCAM-1 and FMD levels and may be an effective adjunctive therapy for improving blood pressure and endothelial function.

Analysis of urine cell-free DNA in bladder cancer diagnosis by emerging bioactive technologies and materials.

Urinary cell-free DNA (UcfDNA) is gaining recognition as an important biomarker for diagnosing bladder cancer. UcfDNA contains tumor derived DNA sequences, making it a viable candidate for non-invasive early detection, diagnosis, and surveillance of bladder cancer. The quantification and qualification of UcfDNA have demonstrated high sensitivity and specificity in the molecular characterization of bladder cancer. However, precise analysis of UcfDNA for clinical bladder cancer diagnosis remains challenging. This review summarizes the history of UcfDNA discovery, its biological properties, and the quantitative and qualitative evaluations of UcfDNA for its clinical significance and utility in bladder cancer patients, emphasizing the critical role of UcfDNA in bladder cancer diagnosis. Emerging bioactive technologies and materials currently offer promising tools for multiple UcfDNA analysis, aiming to achieve more precise and efficient capture of UcfDNA, thereby significantly enhancing diagnostic accuracy. This review also highlights breakthroughs in detection technologies and substrates with the potential to revolutionize bladder cancer diagnosis in clinic.

[Proximal femoral nail antirotation combined with locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures].

OBJECTIVE: To investigate the effect of locking plate internal fixation for the treatment of proximal lateral femoral wall fracture. METHODS: From January 2021 to June 2022, 31 patients with intertrochanteric fractures and lateral wall fractures were treated. Among them, 15 patients were treated with proximal femoral nail antirotation (PFNA) fixation including 3 males and 12 females with an average age of (75.87±7.46) years old;the other 16 patients were treated with 3.5 mm pre-curved screw locking plate fixtion for lateral wall fracture including 4 males and 12 females with an average age of (76.15±9.47) years old. After surgery, the surgical index, tip-apical distance(TAD), postoperative standing weight-bearing time, and fracture reduction were compared between two groups. Postoperative hip function was evaluated according to Harris hip score. RESULTS: All patients were followed up for an average of (12±5) months ranging from 7 to 17 months. The immediate postoperative neck angle ranged from 111° to 132°(119.3±8.3)°. Fracture reduction results were excellent in 11 cases, fair in 2, worse in 1 in PFNA group;excellent in 12, fair in 3, worse in 1 in PFNA+locking plate group. One case of the PFNA group had a spiral blade cut out through the femoral head. There were significant differences in the time of operation, the amount of blood loss during the operation, the length of incision between two groups(P<0.05). There was no significant difference in TAD and postoperative standing weight-bearing time between two groups(P>0.05). There were significant differences in Harris scores at 6 months after surgery between two groups(P<0.05). CONCLUSION: The application of PFNA-assisted locking plate in the treatment of femoral intertrochanteric fractures with lateral wall fractures is effective, and can restore the integrity of lateral wall, improve the stability of PFNA internal fixation, and reduce postoperative complications.

RT-RPA-PfAgo detection platform for one-tube simultaneous typing diagnosis of human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is the most prevalent pathogen contributing to acute respiratory tract infections (ARTI) in infants and young children and can lead to significant financial and medical costs. Here, we developed a simultaneous, dual-gene and ultrasensitive detection system for typing HRSV within 60 minutes that needs only minimum laboratory support. Briefly, multiplex integrating reverse transcription-recombinase polymerase amplification (RT-RPA) was performed with viral RNA extracted from nasopharyngeal swabs as a template for the amplification of the specific regions of subtypes A (HRSVA) and B (HRSVB) of HRSV. Next, the Pyrococcus furiosus Argonaute (PfAgo) protein utilizes small 5'-phosphorylated DNA guides to cleave target sequences and produce fluorophore signals (FAM and ROX). Compared with the traditional gold standard (RT-qPCR) and direct immunofluorescence assay (DFA), this method has the additional advantages of easy operation, efficiency and sensitivity, with a limit of detection (LOD) of 1 copy/µL. In terms of clinical sample validation, the diagnostic accuracy of the method for determining the HRSVA and HRSVB infection was greater than 95%. This technique provides a reliable point-of-care (POC) testing for the diagnosis of HRSV-induced ARTI in children and for outbreak management, especially in resource-limited settings.

[Identification of chemical components in Qinggu San reference sample of classial prescription based on UHPLC-Q/Orbitrap HRMS combined with molecular network technology].

The method of ultra-high performance liquid chromatography-quadrupole-electrostatic field orbitrap high-resolution mass spectrometry(UHPLC-Q/Orbitrap HRMS)combined with molecular network was developed in this study for rapidly analyzing the chemical components of the Qinggu San reference sample of classical prescription. Firstly, an ACQUITY UPLC BEH Shield RP_(18) column(2.1 mm×100 mm, 1.7 µm)was used, and acetonitrile and 0.1% formic acid were taken as the mobile phases for gradient elution. The flow rate was 0.4 mL·min~(-1), and the column temperature was 30 ℃. Under these conditions, the mass spectrum data were collected in both positive and negative ion modes of the heated electrospray ionization source. Subsequently, the mass spectrum data of the Qinggu San reference sample were uploaded to the Global Natural Products Social Molecular Network(GNPS)platform for calculation and analysis, and a visual molecular network was built with Cytoscape 3.8.2 software. On this basis, the chemical components of the Qinggu San reference sample were identified by fragmentation regularity of standard compounds, retention time, accurate relative molecular weight of HR-MS, characteristic fragment ions information, literature, and databases. Finally, a total of 105 chemical components were identified and speculated in the Qinggu San reference sample, including 19 iridoid glycosides, 23 flavonoids, 15 phenylpropanoids, 11 triterpene saponins, and 37 other components. Meanwhile, two of these components are potential new compounds. The method used in this study not only achieved rapid and accurate identification of chemical components in the Qinggu San reference sample and provided a scie-ntific basis for the study of pharmacological substances and quality control of Qinggu San compound preparations but also provided a refe-rence for the rapid identification of chemical components in traditional Chinese medicine compound preparations.

Characteristics and influencing factors of demoralization in patients with lung cancer: A latent class analysis.

OBJECTIVE: Demoralization has garnered increasing attention in recent years as a significant psychological distress. This study aims to identify latent classes of demoralization in lung cancer patients using Latent Class Analysis (LCA) from a person-centered perspective and to explore the factors influencing the latent classes of demoralization. METHODS: A cross-sectional study using convenience sampling was conducted among 567 lung cancer patients in three tertiary hospitals in China. LCA was employed to classify heterogeneous classes of demoralization. Multinomial logistic regression analyses were performed to explore the associations between demographic and clinical characteristics, as well as physical symptoms, resilience, family function, and coping strategies, with class membership in the identified heterogeneous subgroups of lung cancer patients. RESULTS: Three latent classes of demoralization were identified: the high demoralization group (Class 1, 14.8%), the moderate demoralization-distress and helplessness group (Class 2, 37.2%), and the low demoralization group (Class 3, 48.0%). In comparison to Class 3, lung cancer patients with hypertension, higher core symptom burden, poorer resilience, dysfunctional family dynamics, and resignation coping were more likely to belong to Class 1 and Class 2. CONCLUSIONS: The demoralization patterns in lung cancer patients were varied. Targeted intervention should be developed based on the characteristics of each class, and timely attention should be paid to high-risk patients.

Crosstalk of nervous and immune systems in pancreatic cancer.

Pancreatic cancer is a highly malignant tumor known for its extremely low survival rate. The combination of genetic disorders within pancreatic cells and the tumor microenvironment contributes to the emergence and progression of this devastating disease. Extensive research has shed light on the nature of the microenvironmental cells surrounding the pancreatic cancer, including peripheral nerves and immune cells. Peripheral nerves release neuropeptides that directly target pancreatic cancer cells in a paracrine manner, while immune cells play a crucial role in eliminating cancer cells that have not evaded the immune response. Recent studies have revealed the intricate interplay between the nervous and immune systems in homeostatic condition as well as in cancer development. In this review, we aim to summarize the function of nerves in pancreatic cancer, emphasizing the significance to investigate the neural-immune crosstalk during the advancement of this malignant cancer.

Relationships between spirituality and mental stress in people living with HIV in China: A cross-sectional study.

There are limited reports on the relationship between spirituality and mental stress in PLWH in China, who may be subject to anti-religious pressures from the government. In this study, we aimed to understand whether spirituality influences Chinese PLWH's mental stress and, if so, at what level. We recruited 200 PLWHs from Beijing's Ditan Hospital to complete a cross-sectional survey inquiring about their practice of spirituality as well as their level of mental stress. The study found that PLWH who presented with a mid-level of spirituality have the highest mental stress when compared to those who have a low level of spiritual beliefs or a high level of spiritual beliefs. This study points to the utility of healthcare providers taking PLWH's potential spirituality into consideration, perhaps in particular for those with a moderate level of spirituality, in order to provide the most comprehensive care possible.

[Distribution Characteristics and Risk Assessment of Microplastics in Water of Different Functional Parks in Guilin].

The water environment capacity of urban parks is small, and their self-purification ability is poor. They are also more likely to be affected by microplastics (MPs), which cause an imbalance of the water micro-ecosystem. Based on the functional characteristics of parks (comprehensive park, community park, and ecological park), this study investigated the distribution characteristics of MPs in the water of Guilin parks through spot sampling, microscopic observation, and Fourier transform infrared spectroscopy. In addition, the pollution risk index and the pollution load index were used to evaluate the pollution risk of MPs.The results showed that the abundances of MPs in the park surface water and sediments ranged from 104.67-674.44 n·m-3 and 95.57-877.78 n·kg-1, respectively. There were four main shape types of MPs:fragments, fibers, films, and particles. MPs were dominated by fragments and fibers with small sizes (<1 mm). The polymers of MPs were polyethylene and polyethylene terephthalate. There were significant differences in the abundance of MPs in the water of different functional parks, and the abundance of MPs in comprehensive parks was the highest. The abundance of MPs in park water was closely related to the function of the park and the number of people entering the park. The pollution risk of MPs in the surface water of Guilin parks was low, whereas the pollution risk of MPs in sediments was relatively high. The results of this study indicated that tourism was an important source of MPs pollution in the water of Guilin City parks. The pollution risk of MPs in the water of Guilin City parks was mild. However, the pollution risk of MPs accumulated in small freshwater waters of urban parks requires continued attention.

Atypical stromal herpes simplex keratitis: clinical features and diagnosis.

PURPOSE: To report atypical clinical features and diagnosis of stromal herpes simplex keratitis (HSK) and to evaluate the diagnostic efficiency of tear HSV-sIgA in atypical HSK. STUDY DESIGN: Prospective observational study. METHODS: Records of keratitis' patients with tear herpes simplex virus (HSV)-sIgA test results acquired between May 2019 and November 2021 were evaluated retrospectively. Positive tear HSV-sIgA test was used to identify herpes simplex virus (HSV) infection. Patients with typical presentations and histories of HSV keratitis (HSK) were excluded. RESULTS: Eleven eyes of 11 patients initially diagnosed as keratitis caused by other etiology were confirmed as having HSV infection by positive results of tear HSV-sIgA. Clinical features of atypical stromal HSK were variable. Antiviral treatment was effective in all patients. CONCLUSION: The appearance of an atypical stromal HSK represents a diagnostic challenge. Tear HSV-sIgA test could help provide a quick diagnosis.

Understanding factors influencing demoralization among cancer patients based on the bio-psycho-social model: A systematic review.

OBJECTIVE: Demoralization is a prevalent psychological problem among cancer patients and reflects a sense of subjective incompetence. This systematic review aims to identify factors influencing demoralization among cancer patients. METHODS: Eleven databases were systematically searched from database inception to 31 December 2020. Google Scholar and relevant reference lists were supplementarily searched. Studies reporting demoralization measured by Demoralization Scale and its influencing factors among cancer patients were included. A qualitative synthesis was conducted owing to the heterogeneity of the study outcome. RESULTS: A total of 49 studies involving 10,712 participants were included in this review. The results showed substantial effect size variation, but the psychological factors showed the strongest magnitude of association. Among the biological factors, the number of physical symptoms (mean r values [rs]: 0.331) was associated with increased demoralization. Among the psychological factors, negative psychological factors include hopelessness (mean rs: 0.633), desire for death (mean rs: 0.620), dignity-related distress (mean rs: 0.595), depression (mean rs: 0.593), anxiety (mean rs: 0.589), psychological distress (mean rs: 0.465), and suicidal ideation (mean rs: 0.460) were related to increased demoralization; whereas positive psychological factors including hope (mean rs: -0.565), attachment security (mean rs: -0.530), and sense of coherence (mean rs: -0.453) were related to decreased demoralization. Among the social factors, social support (mean rs: -0.330) was negatively related to demoralization, and the demographic factors were still controversial. Quality of life was considered to be at the intersection of biopsychosocial factors and negatively associated with demoralization (mean rs: -0.599). CONCLUSIONS: Demoralization is a consequence of the interaction of physical, psychological, and social factors among cancer patients. Factors with a significant effect should not be overlooked when designing an intervention to reduce demoralization. It is necessary to distinguish demoralization from other negative psychological states and further explore positive psychological factors influencing demoralization among cancer patients.

Barriers and facilitators to uptake of lung cancer screening: A mixed methods systematic review.

Numerous factors contribute to the low adherence to lung cancer screening (LCS) programs. A theory-informed approach to identifying the obstacles and facilitators to LCS uptake is required. This study aimed to identify, assess, and synthesize the available literature at the individual and healthcare provider (HCP) levels based on a social-ecological model and identify gaps to improve practice and policy decision-making. Systematic searches were conducted in nine electronic databases from inception to December 31, 2020. We also searched Google Scholar and manually examined the reference lists of systematic reviews to include relevant articles. Primary studies were scored for quality assessment. Among 3938 potentially relevant articles, 36 studies, including 25 quantitative and 11 qualitative studies, were identified for inclusion in the review. Fifteen common factors were extracted from 34 studies, including nine barriers and six facilitators. The barriers included individual factors (n = 5), health system factors (n = 3), and social/environmental factors (n = 1). The facilitators included only individual factors (n = 6). However, two factors, age and screening harm, remain mixed. This systematic review identified and combined barriers and facilitators to LCS uptake at the individual and HCP levels. The interaction mechanisms among these factors should be further explored, which will allow the construction of tailored LCS recommendations or interventions for the Chinese context.

Barriers and facilitators of lung cancer screening uptake: protocol of a mixed methods systematic review.

INTRODUCTION: The global uptake rates of lung cancer screening (LCS) with low-dose CT remain low. Since numerous factors contribute to the underuse of LCS, a theory-informed approach to identify and address the uptake of LCS barriers and facilitators is required. This study aims to document the methods which were used to identify, appraise, and synthesise the available qualitative, quantitative, and mixed methods evidence, addressing the barriers and facilitators at the individual and healthcare provider level, according to the social-ecological model, before identifying gaps to aid future practices and policies. METHODS AND ANALYSIS: The following databases will be searched: PubMed, Ovid (Journals @ Ovid Full Text and Ovid MEDLINE), EMBASE, CINAHL, PsycINFO, Cochrane Library, Chinese Biomedical Database, Chinese National Knowledge Infrastructure, and Wanfang database, from their creation up to 31 December 2020. Two reviewers will be involved in independently screening, reviewing, and synthesising the data; and calibration exercises will be conducted at each stage. Disagreements between the two reviewers will be resolved by arbitration by a third reviewer. The Critical Appraisal Checklist for Studies Reporting Prevalence Data from the Joanna Briggs Institute, the Critical Appraisal Skills Programme criteria adapted for qualitative studies, and the 16-item Quality Assessment Tool (QATSDD) will be used in the quality assessment of primary studies. We will perform data synthesis using the Review Manager software, V.5.3. ETHICS AND DISSEMINATION: This study is a review of published data and therefore needs no ethical approval. The findings of this systematic review will be published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: CRD42020162802.

Associations of long-term physical activity trajectories with coronary artery calcium progression and cardiovascular disease events: results from the CARDIA study.

OBJECTIVE: The study aimed to assess the associations of physical activity (PA) trajectories across a 25-year span with coronary artery calcium (CAC) progression, and subsequent risk of cardiovascular disease (CVD) events. METHODS: We included 2497 participants from the Coronary Artery Disease Risk Development in Young Adults study who had computed tomography-assessment of CAC at baseline (year 15: 2000-2001) and follow-up (year 20 or 25) and at least three measures of PA from year 0 to year 25. Long-term PA trajectories were determined by latent class modelling using a validated questionnaire. RESULTS: Among the included participants, 1120 (44.9%) were men, 1418 (56.8%) were white, and the mean (SD) age was 40.4 (3.6) years. We identified three distinct PA trajectories based on PA average levels and change patterns: low (below PA guidelines, n=1332; 53.3%); moderate (meeting and slightly over PA guidelines, n=919; 36.8%) and high (about three times PA guidelines or more, n=246; 9.9%). During a mean (SD) follow-up of 8.9 (2.1) years, 640 (25.6%) participants had CAC progression. Participants in the high PA trajectory group had a higher risk of CAC progression than those in the low PA trajectory group after adjustment for traditional cardiovascular risk factors (HR 1.51; 95% CI 1.18 to 1.94). However, high PA trajectory was not associated with an increased risk of incident CVD events (HR 1.01; 95% CI 0.44 to 2.31) and the incidence of CVD events in participants with CAC progression was similar across all three PA trajectory groups (p=0.736). CONCLUSION: Long-term PA about three times the guidelines or more is independently associated with CAC progression; however, no additional risk of incident CVD events could be detected.

Adaptation and validation of the Chinese version of the lung cancer screening health belief scales.

BACKGROUND: Health belief is an important factor affecting lung cancer screening in high-risk population, but the research based on Chinese cultural background is still insufficient. Therefore, we adapted the English version of the Lung Cancer Screening Health Belief Scales (LCSHB) into the Chinese version (LCSHB-C) and examined its psychometric characteristics. METHODS: After obtaining authorization from the original author, the LCSHB-C was adapted based upon Brislin's translation model. Using a variety of community-based recruitment methods, a total of 353 participants were recruited in Fuzhou, Fujian province, China to complete the questionnaires. We combined the classical test theory and item response theory to examine the psychometric properties of the LCSHB-C. RESULTS: The Cronbach's alpha for the four subscales ranged from 0.83 ~ 0.93. The content validity index for the four subscales was ranged from 0.87 ~ 1.0. Confirmatory factor analysis supported each subscale structure model fit well. Rasch analysis results further validated the reliability and validity of the four subscales. The person reliability and separation index of each subscale ranged from 0.77 to 0.87 and 1.83 to 2.63, respectively. CONCLUSIONS: The LCSHB-C is a reliable and valid instrument used to measure health beliefs related to lung cancer screening among those high-risk for lung cancer in China, which facilitates the development of lung cancer screening programs and promotes the "three early prevention strategies" of lung cancer (i.e.,early detection, early diagnosis and early treatment).

Influencing factors of cancer prevention and control among urban and rural adults in Fujian, China: A cross-sectional survey.

Objective: Cancer burden can be reduced when the population's knowledge of cancer prevention and control measures is increased. However, current epidemiological research investigating cancer prevention and control knowledge in China is limited. This study aimed to examine the core knowledge levels of cancer prevention and control measures as well as its influencing factors among adults in Fujian, China. Study design: A cross-sectional study. Methods: From September to December 2021, a total of 2,440 Chinese urban and rural adults from Fujian Province, located in Southeastern China, were randomly selected for this cross-sectional study. The probability proportionate approach to sampling was used. A 38-item questionnaire that covered demographics and basic knowledge of cancer, including concepts, screening, therapy, and rehabilitation-related key points was used to measure knowledge levels of cancer prevention and control measures among 2,074 participants. The level of each participants' core knowledge of cancer prevention and control measures was defined as a rate calculated by the number of correct answers divided by the total number of questions. The binary logistic regression model was used to determine if influencing factors were associated with core knowledge awareness. Results: In total, 1,290 participants (62.2%) were in the low knowledge group and 784 (37.8%) were in the high knowledge group. The average knowledge rate of cancer prevention and control measures among all participants was 56.01%. Participants from urban areas, who held white-collar jobs, were married, had a bachelor's degree or above, had a family history of cancer, or self-rated their health level as good or average were associated with higher rates of cancer prevention and control core knowledge (overall p < 0.05). Conclusion: These findings may assist healthcare providers and/or researchers in designing effective primary preventive interventions to enhance the general population's cancer prevention and control knowledge, and subsequently decrease the cancer burden in China.

[WITHDRAWN] The Impact of Policy and COVID-19 Prevention Strategies in China: A Qualitative Study.

The authors have requested that this preprint be removed from Research Square.

Association of dietary zinc intake with coronary artery calcium progression: the Multi-Ethnic Study of Atherosclerosis (MESA).

PURPOSE: Zinc is considered protective against atherosclerosis; however, the association between dietary zinc intake and cardiovascular disease remains debated. We investigated whether dietary zinc intake was associated with coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis (MESA). METHODS: This analysis included 5186 participants aged 61.9 ± 10.2 years (48.8% men; 41.3% white, 25.0% black, 21.6% Hispanic, and 12.1% Chinese American) from the MESA. Dietary zinc intake was assessed by a self-administered, 120-item food frequency questionnaire at baseline (2000-2002). Baseline and follow-up CAC were measured by computed tomography. CAC progression was defined as CAC > 0 at follow-up for participants with CAC = 0 at baseline; and an annualized change of 10 or percent change of ≥ 10% for those with 0 < CAC < 100 or CAC ≥ 100 at baseline, respectively. RESULTS: Dietary zinc intake was 8.4 ± 4.5 mg/day and 2537 (48.9%) of the included participants had CAC at baseline. Over a median follow-up of 3.4 years (25th-75th percentiles = 2.0-9.1 years), 2704 (52.1%) participants had CAC progression. In the fully adjusted model, higher dietary zinc was associated with a lower risk of CAC progression in both men (hazard ratio [HR] 0.697, 95% confidence interval [CI] 0.553-0.878; p = 0.002) and women (HR 0.675; 95% CI 0.496-0.919; p = 0.012, both comparing extreme groups). Furthermore, such an inverse association was attributable to dietary zinc intake from non-red meat (p < 0.05), rather than red meat sources (p > 0.05). CONCLUSIONS: In this multiethnic population free of clinically apparent cardiovascular disease, higher dietary zinc intake from non-red meat sources was independently associated with a lower risk of CAC progression. CLINICAL TRIAL REGISTRATION NUMBER: The MESA trial was registered at clinicaltrials.gov as NCT00005487.

Interleukin-22 regulating Kupffer cell polarization through STAT3/Erk/Akt crosstalk pathways to extenuate liver fibrosis.

AIMS: Interleukin (IL)-22 activates multiple signaling pathways to exert anti-inflammatory effects, but few studies have examined whether and how IL-22 may shift macrophage polarization between M1 (pro-inflammatory) and M2 (anti-inflammatory) states and thereby influence the progression of hepatic fibrosis. MAIN METHODS: Utilized CCl4 to induce liver fibrosis in mice, detected the role of IL-22 in inhibiting liver fibrosis by regulating Kupffer cells (KCs) polarization in vivo and in vitro. U937 cells were used to confirm the mechanism of IL-22 regulating macrophage polarization via the STAT3/Erk/Akt pathways. Human liver specimens were collected to verify the correlation between the levels of IL-22 and KCs during liver fibrogenesis. KEY FINDINGS: During CCl4-induced liver fibrosis progression in mice, adding exogenous IL-22 significantly inhibited pro-fibrogenic and macrophage phenotype-altering factors secreted by M1-KCs, and it increased the number of M2-KCs. In co-cultures of hepatic stellate cells and KCs from mice treated with IL-22, a high M2/M1-KCs ratio inhibited collagen production and stellate cell activation. These results suggest that IL-22 can increase the ratio of M2-KCs to M1-KCs and thereby attenuate the progression of liver fibrosis. Mechanistic studies in vitro showed that IL-22 promoted polarization of lipopolysaccharide-treated U937 macrophages from M1 to M2. The cytokine exerted these effects by activating the STAT3 pathway while suppressing Erk1/2 and Akt pathways. Furthermore, immunofluorescent staining in human liver specimens confirmed that IL-22 levels positively correlated with the number of M2-KCs during liver fibrogenesis. SIGNIFICANCE: IL-22 regulates the STAT3/Erk/Akt to increase the M2/M1-KCs ratio and thereby slow liver fibrogenesis.

Dynamic changes in the systemic immune responses of spinal cord injury model mice.

Intraspinal inflammatory and immune responses are considered to play central roles in the pathological development of spinal cord injury. This study aimed to decipher the dynamics of systemic immune responses, initiated by spinal cord injury. The spinal cord in mice was completely transected at T8. Changes in the in vivo inflammatory response, between the acute and subacute stages, were observed. A rapid decrease in C-reactive protein levels, circulating leukocytes and lymphocytes, spleen-derived CD4+ interferon-γ+ T-helper cells, and inflammatory cytokines, and a marked increase in neutrophils, monocytes, and CD4+CD25+FOXP3+ regulatory T-cells were observed during the acute phase. These systemic immune alterations were gradually restored to basal levels during the sub-acute phase. During the acute phase of spinal cord injury, systemic immune cells and factors showed significant inhibition; however, this inhibition was transient, and the indicators of these serious disorders gradually returned to baseline levels during the subacute phase. All experiments were performed in accordance with the institutional animal care guidelines, approved by the Institutional Animal Care and Use Committee of Experimental Animal Center of Drum Tower Hospital, China (approval No. 2019AE01040) on June 25, 2019.